Identification and analyses of colitis-associated gene segment using colitis-model mice by CRISPR/Cas9 system.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460972
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kumamoto University
• Principal Investigator: Irie Atsushi 熊本大学, 大学院生命科学研究部(医), 講師 (30250343)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 潰瘍性大腸炎 / HLA-DR / CRISPR/Cas9システム / トランスジェニックマウス / 疾患モデル動物

Outline of Final Research Achievements

The aim of this study is to identify the cause of spontaneous colitis, which homozygotes of HLA-DR4 transgenic mice established by the investigators develop. At the start point, the transgenes were identified to be inserted in the chromosome 3 with the deletion of about 39kb segment. Since only homozygotes develop colitis, either deletion of the 39kb gene segment or higher expression of HLA-DR4 might be involved in the cause of the colitis.
Using CRISPR/Cas9 system, we have successfully established the mice without the 39kb segment, however, those mice did not develop colitis. Therefore, the 39kb segment may have nothing to do with the development of the colitis. On the other hand, the homozygotes of HLA-DR4 transgenic mice with MHC class II transactivator (CIITA) knockout background, which do not express MHC class II molecules including HLA-DR4, did not develop the colitis. Therefore, overexpression of HLA-DR4, not the lack of the 39kb, is involved in the cause of the colitis.

Free Research Field

免疫学